Environmental enrichment restores potentiation in S1 layer 2/3 neurons after perinatal fentanyl exposure. A–D, Time course (left) of STP and LTP (STP/LTP) of EPSCs following paired induction (80 electrical stimulation pulses at 2 Hz paired with postsynaptic depolarization to +30 mV). Bar graphs (right) show group data comparing EPSC amplitudes at baseline −5–0 min (1), STP 0–5 min (2), and LTP 25–30 min (3) after LTP induction. Insets depict sample traces from times indicated on time course graph. A, Within-group comparisons indicate STP and LTP were induced in S1 layer 2/3 neurons from vehicle-exposed, standard-housed mice. B, LTP paired induction parameters induced LTD of the EPSC in fentanyl-exposed, standard-housed mice. C, LTP paired induction protocol failed to further potentiate EPSC amplitude from vehicle-exposed, enriched-housed mice. D, The paired induction protocol induced STP, but not LTP, in fentanyl-exposed, enriched-housed mice. E, Between-group comparisons of the EPSC amplitudes post-LTP induction. Fentanyl-exposed, standard-housed mice had lower EPSC amplitudes than vehicle-exposed, standard-housed mice at 0- to 5- and 25- to 30-min time points. Environmental enrichment increased the EPSC amplitude of fentanyl-exposed, enriched-housed mice, relative to their fentanyl-exposed, standard-housed counterparts also at 0- to 5- and 25- to 30-min time points. F, Between-group comparisons indicate fentanyl-exposed, standard-housed mice had a lower occurrence of neurons that exhibit STP and LTP than vehicle-exposed, standard-housed mice. Raising fentanyl-exposed mice in environmental enrichment increased the proportion of neurons that potentiate. n = 6–8 mice/group, 1 neuron/mouse. Data depict means and 95% confidence intervals.